Here is the honest framing: Isla Mujeres is itself a day trip for most people, so if you are only here two nights you do not need to leave at all. But if you are basing on the island for a few days, a handful of nearby outings earn the boat ride. Ordered by value.
Worth making
MUSA underwater museum and Manchones reef (half-day, about 20–45 minutes by boat)
The best water outing within easy reach. The submerged sculpture park and the shallow Manchones reef sit between the island and Cancún, and a half-day snorkel or dive trip leaves right from the island. Book a small-boat operator, not a party catamaran, and you will actually see the sculptures and coral rather than queue behind fifty people. Verdict: worth it for anyone who likes snorkeling, and central to the area’s diving and snorkeling.
Whale shark grounds (half-day, about 1 to 2 hours offshore, June to August only)
A seasonal open-water trip north of the island to swim alongside whale sharks feeding at the surface. When the season and seas line up it is the standout excursion of the whole region and one of Mexico’s best nature days. Choose an operator that caps swimmers per shark. Verdict: worth it in summer, skip entirely off-season because the sharks are simply gone.
Isla Contoy (full day, about 1.5 to 2 hours by boat)
A protected, uninhabited bird island north of here, reached on a tightly permitted, limited-numbers full-day tour, often combined with a whale shark morning in season. It is genuinely lovely and genuinely a whole day at sea. Verdict: worth it only if wildlife is your priority and the seas are calm; otherwise the day is better spent on Isla Mujeres itself.
Skippable from here
Cancún (ferry plus a short taxi)
Easy to reach for the airport, the malls, or an ADO bus connection onward down the coast. Useful logistically, not somewhere you go for fun from a calmer island. Verdict: an errand, not an outing.
Mainland cenotes and ruins (a long day each way)
Tulum’s ruins, the Riviera Maya cenotes, even Chichén Itzá are technically reachable as marathon day trips, but from an island they mean a ferry, a long drive, and a ferry back. Verdict: skip from here. Save those for when you are actually based on the mainland at Playa del Carmen or Tulum.
A friend’s advice
Do not day-trip yourself off a short island stay. One good small-boat run to MUSA (or a whale shark morning if it is summer) is plenty. The cenotes, ruins and mainland excursions belong to a separate Quintana Roo itinerary, not to the two calm days you came to the island for.